Keytruda (pembrolizumab) is an anticancer drug which has just been authorized by the French National Authority for Health (HAS) for the treatment of triple negative breast cancer, combined with chemotherapy. What are its indications? Its side effects? Its effectiveness on life expectancy?
In a notice published on November 5, 2021, the Haute Autorité de Santé (HAS) has granted an authorization for early post-Marketing Authorization (marketing authorization) to the drug Keytruda® “in combination with chemotherapy in the treatment of adult patients with triple negative breast cancer“. Triple negative breast cancer represents about 14 to 16% cases of breast cancer. He touches mostly younger than average people (50 years on average for triple negative cancer versus 62 years for breast cancer) and is particularly fatal without effective therapy. This medication is already prescribed for many cancers, such as melanoma, Hodgkin’s lymphoma, colorectal cancer … This authorization comes a few weeks later authorization from Trodelvy® (marketed in France since November 1, 2021) also for people with triple negative breast cancer. What are the exact indications for this treatment? How long does it take to improve life expectancy? What are its side effects?
What is the Keytruda drug?
Keytruda® is an anticancer medicine with the active substance pembrolizumab, a monoclonal antibody. This is a medicine reserved for hospital use. Its prescription is reserved for oncology specialists or physicians competent in oncology. This treatment is administered by intravenous infusion in the hospital.
What are the indications?
In a notice of November 5, 2021, HAS announces that Keytruda® (from MSD France laboratory) has received early post-marketing authorization in the indication “in combination with chemotherapy in the treatment of adult patients with triple negative breast cancer locally recurrent unresectable or metastatic, whose tumors express PD-L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease“. This authorization is valid for a period of one year from the date of notification and may be renewed under the conditions provided for in Article R. 5121-69-4 of the Public Health Code. This decision follows the marketing authorization of Keytruda® in the same indication, granted on October 22, 2021 by the European Commission. Its reimbursement must still be validated by Social Security.
In addition, this treatment benefits from a marketing authorization (AMM) for other indications:
- In the treatment ofadvanced melanoma (unresectable or metastatic or stage III with lymph node involvement, having had a complete resection)
- In the first-line treatment of adult patients withmetastatic non-small cell lung cancer
- In the treatment of adult and pediatric patients aged 3 years and older withclassic Hodgkin lymphoma
- In the treatment of adult patients withurothelial carcinoma locally advanced or metastatic
- In the first-line treatment of adult patients with” squamous cell carcinoma of the head and neck metastatic or recurrent unresectable
- In the first-line treatment of adult patients withadvanced renal cell carcinoma
- In the first-line treatment of adult patients withmetastatic colorectal cancer with high microsatellite instability (MSI-H) or DNA mismatch repair system (dMMR) deficiency.
- In the first-line treatment of adult patients withesophageal cancer or adenocarcinoma of the gastroesophageal junction
How effective on life expectancy?
The median overall survival was 23 months in patients treated with Keytruda + chemotherapy.
Triple negative breast cancer is associated with clearly pejorative prognosis, with a median overall survival of around 14 months, and a 5-year survival rate of 11.3%. It’s a crippling disease with a major impact on social, emotional, family and professional life linked in particular pain, deterioration of general condition, chronic fatigue, depression and loss of autonomy. Keytruda would bring, according to HAS, a noticeable improvement in the overall survival of triple negative breast cancer, compared to chemotherapy alone. According to the studies relayed by the HAS, the median overall survival was 23 months in patients treated with Keytruda (pembrolizumab) + chemotherapy versus 16.1 months in patients treated with chemotherapy alone, i.e. an absolute gain of 6.9 months.
What are the side effects ?
Most of the effects are not serious and do not lead to stopping treatment.
The study Keynote-355 conducted in double blind, having compared pembrolizumab in combination with chemotherapy versus chemotherapy alone in adult patients with triple negative breast cancer, shows that pembrolizumab + chemotherapy treatment is linked to a risk of adverse effects. “Most of these effects are not serious and do not lead to treatment discontinuation. The most frequently reported side effects are hypothyroidism (in 15.8% of cases)“, indicates the HAS. The majority of hypothyroidism reported was grade 1-2 and only 6% required treatment with corticosteroids. In addition, atypical responses, that is to say an initial and transient increase in tumor size or the appearance of new small lesions during the first months, followed by regression of the tumor, were observed, reports the HAS. However, in clinically stable patients with initial disease progression, it is recommended to continue treatment until progression is confirmed.
What is the dosage?
“The recommended dose of Keytruda® in adults is either 200 mg every 3 weeks, or 400 mg every 6 weeks, administered by intravenous infusion during 30 minutes“Says HAS. Patients should be treated with Keytruda until disease progression or unacceptable toxicity.
Which laboratory sells Keytruda?
Keytruda® (pembrolizumab) concentrate for solution for infusion is marketed by the company MSD France.
Sources: Early Access Decision, KEYTRUDA (pembrolizumab) – Triple negative breast cancer, November 5, 2021, HAS / Keytruda drug fact sheet, HAS, November 5, 2021.